Comparative effectiveness of preventive treatment with dimethyl fumarate-loaded solid lipid nanoparticles and oral dimethyl fumarate in a mouse model of multiple sclerosis

ElsevierVolume 132, October 2022, 102893Journal of AutoimmunityHighlights•

DMF in SLN can be as effective as free DMF in amelioration of EAE.

DMF in SLN can reach the same effect of free oral drug with reduced administration.

DMF in SLNs didn't alter the proportion lymphocyte subsets.

AbstractBackground

Orally administered dimethyl fumarate (DMF) presents gastrointestinal adverse effects, such as pain and diarrhea, in addition to flushing and lymphopenia.

Objective

Solid lipid nanoparticles (SLNs) with DMF were developed for subcutaneous administration.

Methods

DMF-incorporated SLNs and free DMF were tested in mice induced with experimental autoimmune encephalomyelitis (EAE).

Results

Preventive treatment of free or incorporated DMF were able to reduce the EAE clinical scores, increase the weight of the animals, reduce the lesion area (demyelination and infiltration), reduce microglial fluorescence intensity and reduce the number of microglial cells and astrocytes, when compared to untreated EAE animals. Groups that received DMF had reduced numbers of T cells, B cells and natural killer (NK) cells in the blood, when compared to the non-induced group.

Conclusions

DMF incorporated in SLNs was as effective as free DMF in reducing the clinical scores of the animals, but with reduced administrations when given subcutaneously. In addition, SLN-DMF preventive treatment partially prevented a reduction in the percentages of T and B cells, in the blood, when compared to preventive treatment with free DMF (oral), which suggests reduction of lymphopenia.

Keywords

Dimethyl fumarate

Experimental autoimmune encephalomyelitis

Solid lipid nanoparticles

Subcutaneous route

Multiple sclerosis

AbbreviationsSLNs

solid lipid nanoparticles

EAE

experimental autoimmune encephalomyelitis

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